NCBI Conserved Domain Search

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 175987 [Multi-domain] Cd Length: 162 Bit Score: 265.73 E-value: 8.68e-87

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 399 RGLLALSLKYVPAGSEGA---GLPPSGELHFWVKEARDLLPLRA-GSLDTYVQCFVLPDDSQASRQRTRVVRRSLSPVFN 474
Cdd:cd04020    1 RGELKVALKYVPPESEGAlksKKPSTGELHVWVKEAKNLPALKSgGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 475 HTMVYDGFGPADLRQACAELSLWDHGALA-NRQLGGTRLSLGTGSSYGLQVPWMDSTPEEKQLWQALLEQPCEWVDGLLP 553
Cdd:cd04020   81 HTFVYDGVSPEDLSQACLELTVWDHDKLSsNDFLGGVRLGLGTGKSYGQAVDWMDSTGEEILLWQKMLDNPNSWVEGTLP 160


                 ..
gi 300863107 554 LR 555
Cdd:cd04020  161 LR 162

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176039 [Multi-domain] Cd Length: 125 Bit Score: 235.79 E-value: 9.25e-76

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 267 RGSVHFALHYEPGAAELRVHVIQCQGLAAARRR--RSDPYVKSYLLPDK--QSKRKTAVKKRNLNPVFNETLRYSVPQAE 342
Cdd:cd08393    1 QGSVQFALDYDPKLRELHVHVIQCQDLAAADPKkqRSDPYVKTYLLPDKsnRGKRKTSVKKKTLNPVFNETLRYKVEREE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 300863107 343 LQGRVLSLSVWHRESLGRNIFLGEVEVPLDTWDWG-SEPTWLPLQ 386
Cdd:cd08393   81 LPTRVLNLSVWHRDSLGRNSFLGEVEVDLGSWDWSnTQPTWYPLQ 125

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176056 [Multi-domain] Cd Length: 123 Bit Score: 182.45 E-value: 2.49e-55

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 268 GSVHFALHYEPGAAELRVHVIQCQGLAAA--RRRRSDPYVKSYLLPDK--QSKRKTAVKKRNLNPVFNETLRYSVPQAEL 343
Cdd:cd08521    1 GEIEFSLSYNYKTGSLEVHIKECRNLAYAdeKKKRSNPYVKVYLLPDKskQSKRKTSVKKNTTNPVFNETLKYHISKSQL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 300863107 344 QGRVLSLSVWHRESLGRNIFLGEVEVPLDTWDWGSE-PTWLPL 385
Cdd:cd08521   81 ETRTLQLSVWHHDRFGRNTFLGEVEIPLDSWDLDSQqSEWYPL 123

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 175995 [Multi-domain] Cd Length: 125 Bit Score: 155.67 E-value: 2.91e-45

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 268 GSVHFALHYEPGAAELRVHVIQCQGLAAA--RRRRSDPYVKSYLLPDK--QSKRKTAVKKRNLNPVFNETLRYSVPQAEL 343
Cdd:cd04029    2 GEILFSLSYDYKTQSLNVHVKECRNLAYGdeAKKRSNPYVKTYLLPDKsrQSKRKTSIKRNTTNPVYNETLKYSISHSQL 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 300863107 344 QGRVLSLSVWHRESLGRNIFLGEVEVPLDTWDWGS-EPTWLPLQ 386
Cdd:cd04029   82 ETRTLQLSVWHYDRFGRNTFLGEVEIPLDSWNFDSqHEECLPLH 125

C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. Little is known about the expression or localization of Slp3. The C2A domain of Slp3 is Ca2+ dependent. It has been demonstrated that Slp3 promotes dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176038 [Multi-domain] Cd Length: 128 Bit Score: 116.85 E-value: 6.39e-31

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 268 GSVHFALHYEPGAAELRVHVIQCQGLA--AARRRRSDPYVKSYLLPDK--QSKRKTAVKKRNLNPVFNETLRYSVPQAEL 343
Cdd:cd08392    2 GEIEFALHYNFRTSCLEITIKACRNLAygDEKKKKCHPYVKVCLLPDKshNSKRKTAVKKGTVNPVFNETLKYVVEADLL 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 300863107 344 QGRVLSLSVWHRESLGRNIFLGEVEVPLDTWDWGSEPT----WLPL 385
Cdd:cd08392   82 SSRQLQVSVWHSRTLKRRVFLGEVLIPLADWDFEDTDSqrflWYPL 127

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 111.26 E-value: 2.76e-29

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107  283 LRVHVIQCQGLAAA-RRRRSDPYVKSYLLPDKQsKRKTAVKKRNLNPVFNETLRYSVPqaELQGRVLSLSVWHRESLGRN 361
Cdd:pfam00168   3 LTVTVIEAKNLPPKdGNGTSDPYVKVYLLDGKQ-KKKTKVVKNTLNPVWNETFTFSVP--DPENAVLEIEVYDYDRFGRD 79

                          90       100
                  ....*....|....*....|....*
gi 300863107  362 IFLGEVEVPLDTWDWGSEPT-WLPL 385
Cdd:pfam00168  80 DFIGEVRIPLSELDSGEGLDgWYPL 104

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176031 [Multi-domain] Cd Length: 124 Bit Score: 110.05 E-value: 1.52e-28

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 267 RGSVHFALHYEPGAAELRVHVIQCQGLAAARRR-RSDPYVKSYLLPDKQSKRKTAVKKRNLNPVFNETLRYSVPQAELQG 345
Cdd:cd08385    2 LGKLQFSLDYDFQSNQLTVGIIQAADLPAMDMGgTSDPYVKVYLLPDKKKKFETKVHRKTLNPVFNETFTFKVPYSELGN 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 300863107 346 RVLSLSVWHRESLGRNIFLGEVEVPLDTWDWGSE-PTWLPLQP 387
Cdd:cd08385   82 KTLVFSVYDFDRFSKHDLIGEVRVPLLTVDLGHVtEEWRDLES 124

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176027 [Multi-domain] Cd Length: 122 Bit Score: 109.30 E-value: 2.40e-28

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 268 GSVHFALHYEPGAaeLRVHVIQCQGLAAARRRRSDPYVKSYLLPD--KQSKRKTAVKKRNLNPVFNETLRYS-VPQAELQ 344
Cdd:cd08381    2 GQVKLSISYKNGT--LFVMVMHAKNLPLLDGSDPDPYVKTYLLPDpqKTTKRKTKVVRKTRNPTFNEMLVYDgLPVEDLQ 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 300863107 345 GRVLSLSVWHRESLGRNIFLGEVEVPLDTWDWGSEPT-WLPL 385
Cdd:cd08381   80 QRVLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQETEkWYPL 121

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 104.72 E-value: 1.03e-26

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 267 RGSVHFALHYEPGAAELRVHVIQCQGLAAAR-RRRSDPYVKSYLLPDKQSKRKTAVKKRNLNPVFNETLRYS-VPQAELQ 344
Cdd:cd08386    2 LGRIQFSVSYDFQESTLTLKILKAVELPAKDfSGTSDPFVKIYLLPDKKHKLETKVKRKNLNPHWNETFLFEgFPYEKLQ 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 300863107 345 GRVLSLSVWHRESLGRNIFLGEVEVPLDTWDWGSEPT-WLPLQP 387
Cdd:cd08386   82 QRVLYLQVLDYDRFSRNDPIGEVSLPLNKVDLTEEQTfWKDLKP 125

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 97.91 E-value: 1.80e-24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAAA-RRRRSDPYVKSYLLPDKqsKRKTAVKKRNLNPVFNETLRYSVPqaELQGRVLSLSVWHRESLGRN 361
Cdd:cd00030    1 LRVTVIEARNLPAKdLNGKSDPYVKVSLGGKQ--KFKTKVVKNTLNPVWNETFEFPVL--DPESDTLTVEVWDKDRFSKD 76

                         90       100
                 ....*....|....*....|....*.
gi 300863107 362 IFLGEVEVPLDTWDWGSEPT--WLPL 385
Cdd:cd00030   77 DFLGEVEIPLSELLDSGKEGelWLPL 102

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175996 [Multi-domain] Cd Length: 127 Bit Score: 98.50 E-value: 2.24e-24

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 266 VRGSVHFALHYEPGAAELRVHVIQCQGLAAARRRR-SDPYVKSYLLPDKQ--SKRKTAVKKRNLNPVFNETLRYSVPQAE 342
Cdd:cd04030    1 PLGRIQLTIRYSSQRQKLIVTVHKCRNLPPCDSSDiPDPYVRLYLLPDKSksTRRKTSVKKDNLNPVFDETFEFPVSLEE 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 300863107 343 LQGRVLSLSVWHRESL--GRNIFLGEVEVPLDTWD 375
Cdd:cd04030   81 LKRRTLDVAVKNSKSFlsREKKLLGQVLIDLSDLD 115

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 94.86 E-value: 1.95e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107   283 LRVHVIQCQGLAAARR-RRSDPYVKSYLLPDKQSKRKTAVKKRNLNPVFNETLRYSVPqaELQGRVLSLSVWHRESLGRN 361
Cdd:smart00239   2 LTVKIISARNLPPKDKgGKSDPYVKVSLDGDPKEKKKTKVVKNTLNPVWNETFEFEVP--PPELAELEIEVYDKDRFGRD 79

                           90
                   ....*....|..
gi 300863107   362 IFLGEVEVPLDT 373
Cdd:smart00239  80 DFIGQVTIPLSD 91

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 175975 [Multi-domain] Cd Length: 134 Bit Score: 95.34 E-value: 3.41e-23

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 268 GSVHFALHYEPGAAELRVHVIQCQGLAA-ARRRRSDPYVKSYLLPD--KQSKRKTAVKKRNLNPVFNETLRYSVPQAELQ 344
Cdd:cd00276    1 GELLLSLSYLPTAERLTVVVLKARNLPPsDGKGLSDPYVKVSLLQGgkKLKKKKTSVKKGTLNPVFNEAFSFDVPAEQLE 80

                         90       100
                 ....*....|....*....|....*....
gi 300863107 345 GRVLSLSVWHRESLGRNIFLGEVEVPLDT 373
Cdd:cd00276   81 EVSLVITVVDKDSVGRNEVIGQVVLGPDS 109

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176036 [Multi-domain] Cd Length: 123 Bit Score: 92.71 E-value: 2.01e-22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 268 GSVHFALHYEPGAAELRVHVIQCQGLAA--ARRRRSDPYVKSYLLPDKQSKRKTAVKKRNLNPVFNETLRYSVPQAELQG 345
Cdd:cd08390    1 GRLWFSVQYDLEEEQLTVSLIKARNLPPrtKDVAHCDPFVKVCLLPDERRSLQSKVKRKTQNPNFDETFVFQVSFKELQR 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 300863107 346 RVLSLSVWHRESLGRNIFLGEVEVPLDTWDWGSEPT-WLPLQP 387
Cdd:cd08390   81 RTLRLSVYDVDRFSRHCIIGHVLFPLKDLDLVKGGVvWRDLEP 123

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.

Pssm-ID: 175997 [Multi-domain] Cd Length: 125 Bit Score: 90.77 E-value: 1.14e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 268 GSVHFALHYEPGAAELRVHVIQCQGLAAARRRR-SDPYVKSYLLPDK--QSKRKTAVKKRNLNPVFNETLRYS-VPQAEL 343
Cdd:cd04031    3 GRIQIQLWYDKVTSQLIVTVLQARDLPPRDDGSlRNPYVKVYLLPDRseKSKRRTKTVKKTLNPEWNQTFEYSnVRRETL 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 300863107 344 QGRVLSLSVWHRESLGRNIFLGEVEVPLDTWDWGSEPTWLPLQ 386
Cdd:cd04031   83 KERTLEVTVWDYDRDGENDFLGEVVIDLADALLDDEPHWYPLQ 125

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176030 [Multi-domain] Cd Length: 133 Bit Score: 90.48 E-value: 1.47e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 282 ELRVHVIQCQGLAAARRRR-SDPYVKSYLLPD--KQSKRKTAVKKRNLNPVFNETLRYSVPQAELQGRVLSLSVWHREsL 358
Cdd:cd08384   14 GLIVGIIRCVNLAAMDANGySDPFVKLYLKPDagKKSKHKTQVKKKTLNPEFNEEFFYDIKHSDLAKKTLEITVWDKD-I 92

                         90
                 ....*....|.
gi 300863107 359 GR-NIFLGEVE 368
Cdd:cd08384   93 GKsNDYIGGLQ 103

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 86.27 E-value: 4.98e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAAARRRRSDPYVK-SYLLPDKQSKRKTAVKKRNLNPVFNETL-------------RYSVPQAELQGRVL 348
Cdd:cd08675    1 LSVRVLECRDLALKSNGTCDPFARvTLNYSSKTDTKRTKVKKKTNNPRFDEAFyfeltigfsyekkSFKVEEEDLEKSEL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 300863107 349 SLSVWHRESLGRNIFLGEVEVPLDTWD-WGSEPTWLPLQPR 388
Cdd:cd08675   81 RVELWHASMVSGDDFLGEVRIPLQGLQqAGSHQAWYFLQPR 121

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176027 [Multi-domain] Cd Length: 122 Bit Score: 85.04 E-value: 9.71e-20

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 422 GELHFWVKEARDLLPLRAGSLDTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTMVYDGFGPADLRQACAELSLWDHGA 501
Cdd:cd08381   13 GTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDLQQRVLQVSVWSHDS 92

                         90
                 ....*....|....
gi 300863107 502 L-ANRQLGGTRLSL 514
Cdd:cd08381   93 LvENEFLGGVCIPL 106

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176033 [Multi-domain] Cd Length: 124 Bit Score: 83.99 E-value: 2.15e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 266 VRGSVHFALHYEPGAAELRVHVIQCQGLAAarRRRS---DPYVKSYLLPDKQSKRKTAVKKRNLNPVFNETLRYSVPQAE 342
Cdd:cd08387    1 TRGELHFSLEYDKDMGILNVKLIQARNLQP--RDFSgtaDPYCKVRLLPDRSNTKQSKIHKKTLNPEFDESFVFEVPPQE 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 300863107 343 LQGRVLSLSVWHRESLGRNIFLGEVEVPLDTWDWgSEPT--WLPLQP 387
Cdd:cd08387   79 LPKRTLEVLLYDFDQFSRDECIGVVELPLAEVDL-SEKLdlWRKIQS 124

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176000 [Multi-domain] Cd Length: 123 Bit Score: 81.56 E-value: 1.65e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 267 RGSVHFALHYEPGAAELRVHVIQCQGLAA-ARRRRSDPYVKSYLLP--DKQSKRKTAVKKRNLNPVFNETLRY-SVPQAE 342
Cdd:cd04035    1 LGTLEFTLLYDPANSALHCTIIRAKGLKAmDANGLSDPYVKLNLLPgaSKATKLRTKTVHKTRNPEFNETLTYyGITEED 80

                         90       100
                 ....*....|....*....|....*....
gi 300863107 343 LQGRVLSLSVWHRESLGrNIFLGEVEVPL 371
Cdd:cd04035   81 IQRKTLRLLVLDEDRFG-NDFLGETRIPL 108

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176034 [Multi-domain] Cd Length: 128 Bit Score: 81.63 E-value: 1.93e-18

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 267 RGSVHFALHYEPGAAELRVHVIQCQGLAAARRRR--SDPYVKSYLLPDKQSKRKTAVKKRNLNPVFNETLR-YSVPQAEL 343
Cdd:cd08388    2 LGTLFFSLRYNSEKKALLVNIIECRDLPAMDEQSgtSDPYVKLQLLPEKEHKVKTRVLRKTRNPVYDETFTfYGIPYNQL 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 300863107 344 QGRVLSLSVWHRESLGRNIFLGEVEVPLDTWDWGSEPT---WLPLQP 387
Cdd:cd08388   82 QDLSLHFAVLSFDRYSRDDVIGEVVCPLAGADLLNEGEllvSREIQP 128

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176050 [Multi-domain] Cd Length: 136 Bit Score: 79.38 E-value: 1.52e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 267 RGSVHFALHYEPGAAELRVHVIQCQGLAAAR-RRRSDPYVKSYLL-PDKQ-SKRKTAVKKRNLNPVFNETLRYSVPQAEL 343
Cdd:cd08405    1 RGELLLSLCYNPTANRITVNIIKARNLKAMDiNGTSDPYVKVWLMyKDKRvEKKKTVIKKRTLNPVFNESFIFNIPLERL 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 300863107 344 QGRVLSLSVWHRESLGRN-----IFLGEVEVPLDTWDW 376
Cdd:cd08405   81 RETTLIITVMDKDRLSRNdligkIYLGWKSGGLELKHW 118

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176047 [Multi-domain] Cd Length: 136 Bit Score: 76.29 E-value: 1.92e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 268 GSVHFALHYEPGAAELRVHVIQCQGLaaarrRR------SDPYVKSYLLPD--KQSKRKTAVKKRNLNPVFNETLRYSVP 339
Cdd:cd08402    2 GDICFSLRYVPTAGKLTVVILEAKNL-----KKmdvgglSDPYVKIHLMQNgkRLKKKKTTIKKRTLNPYYNESFSFEVP 76

                         90       100
                 ....*....|....*....|....*...
gi 300863107 340 QAELQGRVLSLSVWHRESLGRNIFLGEV 367
Cdd:cd08402   77 FEQIQKVHLIVTVLDYDRIGKNDPIGKV 104

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

Pssm-ID: 175992 [Multi-domain] Cd Length: 131 Bit Score: 74.61 E-value: 5.76e-16

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 267 RGSVHFALHYEPGaaELRVHVIQCQ--------GLaaarrrrSDPYVKSYLLPD--KQSKRKTAVKKRNLNPVFNETLRY 336
Cdd:cd04026    1 RGRIYLKISVKDN--KLTVEVREAKnlipmdpnGL-------SDPYVKLKLIPDpkNETKQKTKTIKKTLNPVWNETFTF 71

                         90       100
                 ....*....|....*....|....*....
gi 300863107 337 SVPQAELQGRvLSLSVWHRESLGRNIFLG 365
Cdd:cd04026   72 DLKPADKDRR-LSIEVWDWDRTTRNDFMG 99

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 73.12 E-value: 9.57e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107  422 GELHFWVKEARDLLPL-RAGSLDTYVQCFVLpddSQASRQRTRVVRRSLSPVFNHTMVYDGFgpaDLRQACAELSLWDHG 500
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKdGNGTSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFSVP---DPENAVLEIEVYDYD 74

                          90       100
                  ....*....|....*....|....*....
gi 300863107  501 ALANRQ-LGGTRLSLGTGSSYGLQVPWMD 528
Cdd:pfam00168  75 RFGRDDfIGEVRIPLSELDSGEGLDGWYP 103

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176000 [Multi-domain] Cd Length: 123 Bit Score: 73.47 E-value: 1.09e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 399 RGLLALSLKYVPAGSEgaglppsgeLHFWVKEARDLLPLRAGSL-DTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTM 477
Cdd:cd04035    1 LGTLEFTLLYDPANSA---------LHCTIIRAKGLKAMDANGLsDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETL 71

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 300863107 478 VYDGFGPADLRQACAELSLWDHGALANRQLGGTRLSL 514
Cdd:cd04035   72 TYYGITEEDIQRKTLRLLVLDEDRFGNDFLGETRIPL 108

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176048 [Multi-domain] Cd Length: 134 Bit Score: 72.16 E-value: 4.05e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 268 GSVHFALHYEPGAAELRVHVIQCQGLAAAR-RRRSDPYVKSYLLPD--KQSKRKTAVKKRNLNPVFNETLRYSVPQAELQ 344
Cdd:cd08403    1 GELMFSLCYLPTAGRLTLTIIKARNLKAMDiTGFSDPYVKVSLMCEgrRLKKKKTSVKKNTLNPTYNEALVFDVPPENVD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 300863107 345 GRVLSLSVWHRESLGRNIFLGEVEVPLDTWDWGSEpTWLPL--QPRVP 390
Cdd:cd08403   81 NVSLIIAVVDYDRVGHNELIGVCRVGPNADGQGRE-HWNEMlaNPRKP 127

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175976 [Multi-domain] Cd Length: 133 Bit Score: 71.89 E-value: 5.62e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 267 RGSVHFALHYEPGAAELRVHVIQCQGLAAARRR-RSDPYVKSYLLPD----KQSKRKTAVKKRNLNPVFNETLRYSVP-- 339
Cdd:cd04009    2 YGVLTVKAYYRASEQSLRVEILNARNLLPLDSNgSSDPFVKVELLPRhlfpDVPTPKTQVKKKTLFPLFDESFEFNVPpe 81

                         90       100       110
                 ....*....|....*....|....*....|...
gi 300863107 340 QAELQGRVLSLSVWHRESLGRNIFLGEVEVPLD 372
Cdd:cd04009   82 QCSVEGALLLFTVKDYDLLGSNDFEGEAFLPLN 114

C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 12, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 13, do not have any consensus Ca2+ binding sites. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176051 [Multi-domain] Cd Length: 136 Bit Score: 71.75 E-value: 6.39e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 268 GSVHFALHYEPGAAELRVHVIQCQGLAAARRR-RSDPYVKSYLLPD--KQSKRKTAVKKRNLNPVFNETLRYSVPQAELQ 344
Cdd:cd08406    2 GEILLSLSYLPTAERLTVVVVKARNLVWDNGKtTADPFVKVYLLQDgrKISKKKTSVKRDDTNPIFNEAMIFSVPAIVLQ 81

                         90       100
                 ....*....|....*....|...
gi 300863107 345 GRVLSLSVWHRESLGRNIFLGEV 367
Cdd:cd08406   82 DLSLRVTVAESTEDGKTPNVGHV 104

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176049 [Multi-domain] Cd Length: 136 Bit Score: 71.30 E-value: 1.02e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 267 RGSVHFALHYEPGAAELRVHVIQCQGLAAARRR-RSDPYVKSYLLPDKQ--SKRKTAVKKRNLNPVFNETLRYSVPQAEL 343
Cdd:cd08404    1 RGELLLSLCYQPTTNRLTVVVLKARHLPKMDVSgLADPYVKVNLYYGKKriSKKKTHVKKCTLNPVFNESFVFDIPSEEL 80

                         90       100
                 ....*....|....*....|....*
gi 300863107 344 QGRVLSLSVWHRESLGRNIFLGEVE 368
Cdd:cd08404   81 EDISVEFLVLDSDRVTKNEVIGRLV 105

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.

Pssm-ID: 175997 [Multi-domain] Cd Length: 125 Bit Score: 69.97 E-value: 1.89e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 431 ARDLLPLRAGSL-DTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTMVYDGFGPADLRQACAELSLWD-HGALANRQLG 508
Cdd:cd04031   25 ARDLPPRDDGSLrNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSNVRRETLKERTLEVTVWDyDRDGENDFLG 104


                 ....*....
gi 300863107 509 GTRLSLGTG 517
Cdd:cd04031  105 EVVIDLADA 113

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA3 contains an N-terminal C2 domain, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 175977 [Multi-domain] Cd Length: 148 Bit Score: 69.73 E-value: 3.73e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAAaRRRRSDPYVKSYLL--PDKQSKRKTAVKKRNLNPVFNETL-------------RYSVPQAELQGRV 347
Cdd:cd04010    2 LSVRVIECSDLAL-KNGTCDPYASVTLIysNKKQDTKRTKVKKKTNNPQFDEAFyfdvtidsspekkQFEMPEEDAEKLE 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 300863107 348 LSLSVWHRESLGRNIFLGEVEVPLDTWD--WGSEPTWLPLQPR 388
Cdd:cd04010   81 LRVDLWHASMGGGDVFLGEVRIPLRGLDlqAGSHQAWYFLQPR 123

C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium and this is indeed the case here. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176035 [Multi-domain] Cd Length: 124 Bit Score: 64.95 E-value: 1.22e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 268 GSVHFALHYEPGAAELRVHVIQCQGLAAARRRRSDPY-VKSYLLPDKQSKRKTAVKKRNlNPVFNETLRYS-VPQAELQG 345
Cdd:cd08389    3 GDLDVAFEYDPSARKLTVTVIRAQDIPTKDRGGASSWqVHLVLLPSKKQRAKTKVQRGP-NPVFNETFTFSrVEPEELNN 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 300863107 346 RVLSLSVWHRESLGRNIFLGEVEVPLDTWDWGSE-PTWLPLQP 387
Cdd:cd08389   82 MALRFRLYGVERMRKERLIGEKVVPLSQLNLEGEtTVWLTLEP 124

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

Pssm-ID: 175992 [Multi-domain] Cd Length: 131 Bit Score: 63.43 E-value: 4.81e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 421 SGELHFWVKEARDLLPLRAGSL-DTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTMVYDgFGPADL-RQACAELSLWD 498
Cdd:cd04026   12 DNKLTVEVREAKNLIPMDPNGLsDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFD-LKPADKdRRLSIEVWDWD 90

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176030 [Multi-domain] Cd Length: 133 Bit Score: 62.75 E-value: 8.41e-12

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 404 LSLKYVPAgsegaglppSGELHFWVKEARDLLPLRA-GSLDTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTMVYDgF 482
Cdd:cd08384    4 VSLMYNTQ---------RRGLIVGIIRCVNLAAMDAnGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYD-I 73

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 300863107 483 GPADLRQACAELSLWDHG-ALANRQLGGTRLSLGTGSSYGLQvpWMD--STPEEK-QLWQAL 540
Cdd:cd08384   74 KHSDLAKKTLEITVWDKDiGKSNDYIGGLQLGINAKGERLRH--WLDclKNPDKKiEAWHTL 133

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.

Pssm-ID: 176005 [Multi-domain] Cd Length: 115 Bit Score: 60.27 E-value: 3.62e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAAARRR-RSDPYVKSYLlpDKQSKRKTAVKKRNLNPVFNETLrySVPQAELQGRVLSLSVWHRESLGRN 361
Cdd:cd04040    1 LTVDVISAENLPSADRNgKSDPFVKFYL--NGEKVFKTKTIKKTLNPVWNESF--EVPVPSRVRAVLKVEVYDWDRGGKD 76

                         90
                 ....*....|
gi 300863107 362 IFLGEVEVPL 371
Cdd:cd04040   77 DLLGSAYIDL 86

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176055 [Multi-domain] Cd Length: 135 Bit Score: 60.67 E-value: 4.70e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 268 GSVHFALHYEPGAAELRVHVIQC-QGLAAARRRRSDPYVKSYLLPDKQ--SKRKTAVKKRNLNPVFNETLRYSVPQAELQ 344
Cdd:cd08410    1 GELLLSLNYLPSAGRLNVDIIRAkQLLQTDMSQGSDPFVKIQLVHGLKliKTKKTSCMRGTIDPFYNESFSFKVPQEELE 80

                         90       100
                 ....*....|....*....|...
gi 300863107 345 GRVLSLSVWHRESLGRNIFLGEV 367
Cdd:cd08410   81 NVSLVFTVYGHNVKSSNDFIGRI 103

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 175975 [Multi-domain] Cd Length: 134 Bit Score: 58.36 E-value: 2.90e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 400 GLLALSLKYvpagsegagLPPSGELHFWVKEARDLLPLRA-GSLDTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTMV 478
Cdd:cd00276    1 GELLLSLSY---------LPTAERLTVVVLKARNLPPSDGkGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFS 71

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 300863107 479 YDgFGPADLRQACAELSLWDHGALA-NRQLGGTRLSLgtgssyglqvpwmDSTPEEKQLWQALLEQP----CEW 547
Cdd:cd00276   72 FD-VPAEQLEEVSLVITVVDKDSVGrNEVIGQVVLGP-------------DSGGEELEHWNEMLASPrkpiARW 131

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 57.11 E-value: 3.73e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107   424 LHFWVKEARDLLPL-RAGSLDTYVQCFVLPDDSQasRQRTRVVRRSLSPVFNHTMVYDGFGPADlrqACAELSLWDHGAL 502
Cdd:smart00239   2 LTVKIISARNLPPKdKGGKSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPPPEL---AELEIEVYDKDRF 76

                           90
                   ....*....|...
gi 300863107   503 -ANRQLGGTRLSL 514
Cdd:smart00239  77 gRDDFIGQVTIPL 89

C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176054 [Multi-domain] Cd Length: 137 Bit Score: 57.73 E-value: 5.29e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 267 RGSVHFALHYEPGAAELRVHVIQCQGLAAARRRRSDPYVK-SYLLPDKQSKRK-TAVKKRNLNPVFNETLRYSVPQAELQ 344
Cdd:cd08409    1 LGDIQISLTYNPTLNRLTVVVLRARGLRQLDHAHTSVYVKvSLMIHNKVVKTKkTEVVDGAASPSFNESFSFKVTSRQLD 80

                         90       100
                 ....*....|....*....|....*
gi 300863107 345 GRVLSLSVWHRESLGRNIFLGEVEV 369
Cdd:cd08409   81 TASLSLSVMQSGGVRKSKLLGRVVL 105

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176003 [Multi-domain] Cd Length: 145 Bit Score: 57.72 E-value: 6.35e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAAARRRRSDPYVKSYLlpDKQSKrKTAVKKRNLNPVFNETLRYSVPQAELqgrVLSLSVWHRESLGRNI 362
Cdd:cd04038    4 LKVRVVRGTNLAVRDFTSSDPYVVLTL--GNQKV-KTRVIKKNLNPVWNEELTLSVPNPMA---PLKLEVFDKDTFSKDD 77


                 ....*....
gi 300863107 363 FLGEVEVPL 371
Cdd:cd04038   78 SMGEAEIDL 86

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 175978 [Multi-domain] Cd Length: 111 Bit Score: 55.66 E-value: 1.56e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 278 PGAAELRVHVIQCQGLAAARrrrSDPYVKSYLLPDKQSkrkTAVKKRNLNPVFNETL--RYSVPQAELQGRVLSLSVWHR 355
Cdd:cd04011    1 PQDFQVRVRVIEARQLVGGN---IDPVVKVEVGGQKKY---TSVKKGTNCPFYNEYFffNFHESPDELFDKIIKISVYDS 74

                         90
                 ....*....|....*...
gi 300863107 356 ESLGRNIFLGEVEVPLDT 373
Cdd:cd04011   75 RSLRSDTLIGSFKLDVGT 92

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.

Pssm-ID: 176037 [Multi-domain] Cd Length: 121 Bit Score: 54.99 E-value: 3.30e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAAARRR-------RSDPYVKSYLLPdkqSKRKTAVKKRNLNPVFNETLRYSVPQAElqGRVLSLSVWHr 355
Cdd:cd08391    3 LRIHVIEAQDLVAKDKFvgglvkgKSDPYVIVRVGA---QTFKSKVIKENLNPKWNEVYEAVVDEVP--GQELEIELFD- 76

                         90       100       110
                 ....*....|....*....|....*....|..
gi 300863107 356 ESLGRNIFLGEVEVPL-DTWDWGSEPTWLPLQ 386
Cdd:cd08391   77 EDPDKDDFLGRLSIDLgSVEKKGFIDEWLPLE 108

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.

Pssm-ID: 175989 [Multi-domain] Cd Length: 127 Bit Score: 55.04 E-value: 3.93e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAaarrRR-----SDPYVKSYLlpDKQsKRKTAVKKRNLNPVFNETLRYSVPQAE-LQGRVLSLSVWHRE 356
Cdd:cd04022    2 LVVEVVDAQDLM----PKdgqgsSSAYVELDF--DGQ-KKRTRTKPKDLNPVWNEKLVFNVSDPSrLSNLVLEVYVYNDR 74

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 300863107 357 SLGR-NIFLGEVEVPLDTWDWGSE--PTWLPLQPR 388
Cdd:cd04022   75 RSGRrRSFLGRVRISGTSFVPPSEavVQRYPLEKR 109

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 175990 [Multi-domain] Cd Length: 128 Bit Score: 54.74 E-value: 4.73e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAAARRRR---SDPYVksyLLPDKQSKRKTAVKKRNLNPVFNETlrYSVPQAELQGRVLSLSVWHRESLG 359
Cdd:cd04024    3 LRVHVVEAKDLAAKDRSGkgkSDPYA---ILSVGAQRFKTQTIPNTLNPKWNYW--CEFPIFSAQNQLLKLILWDKDRFA 77

                         90       100       110
                 ....*....|....*....|....*....|.
gi 300863107 360 RNIFLGEVEVPLD----TWDWGSEPTWLPLQ 386
Cdd:cd04024   78 GKDYLGEFDIALEevfaDGKTGQSDKWITLK 108

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176016 [Multi-domain] Cd Length: 125 Bit Score: 54.54 E-value: 5.62e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 282 ELRVHVIQCQGLAAARR-RRSDPYVKSYLlpDKQSKRKTAV-KKRNLNPVFNETLRYSVPQAELQ--GRVLSLSVWHRES 357
Cdd:cd04051    1 TLEITIISAEDLKNVNLfGKMKVYAVVWI--DPSHKQSTPVdRDGGTNPTWNETLRFPLDERLLQqgRLALTIEVYCERP 78

                         90
                 ....*....|....
gi 300863107 358 LGRNIFLGEVEVPL 371
Cdd:cd04051   79 SLGDKLIGEVRVPL 92

C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.

Pssm-ID: 175994 [Multi-domain] Cd Length: 146 Bit Score: 54.70 E-value: 6.03e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 268 GSVHFALHYEPGAaeLRVHVIQCQGLAAARRRR--SDPYVKSYLLPDKQ--SKRKTAVKKRNLNPVFNETLRYSVPQael 343
Cdd:cd04028   18 GDIQLGLYDKKGQ--LEVEVIRARGLVQKPGSKvlPAPYVKVYLLEGKKciAKKKTKIARKTLDPLYQQQLVFDVSP--- 92

                         90       100       110
                 ....*....|....*....|....*....|...
gi 300863107 344 QGRVLSLSVW-HRESLGRNIFLGEVEVPLDTWD 375
Cdd:cd04028   93 TGKTLQVIVWgDYGRMDKKVFMGVAQILLDDLD 125

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176056 [Multi-domain] Cd Length: 123 Bit Score: 53.80 E-value: 7.33e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 420 PSGELHFWVKEARDLL---PLRAGSlDTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTMVYDgFGPADLRQACAELSL 496
Cdd:cd08521   12 KTGSLEVHIKECRNLAyadEKKKRS-NPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYH-ISKSQLETRTLQLSV 89

                         90       100
                 ....*....|....*....|
gi 300863107 497 WDHGALANRQ-LGGTRLSLG 515
Cdd:cd08521   90 WHHDRFGRNTfLGEVEIPLD 109

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 53.22 E-value: 8.76e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 424 LHFWVKEARDLLPLRA-GSLDTYVQCFVLPDdsqaSRQRTRVVRRSLSPVFNHTMVydgFGPADLRQACAELSLWDHGAL 502
Cdd:cd00030    1 LRVTVIEARNLPAKDLnGKSDPYVKVSLGGK----QKFKTKVVKNTLNPVWNETFE---FPVLDPESDTLTVEVWDKDRF 73

                         90
                 ....*....|...
gi 300863107 503 -ANRQLGGTRLSL 514
Cdd:cd00030   74 sKDDFLGEVEIPL 86

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the C2 domain. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176067 [Multi-domain] Cd Length: 119 Bit Score: 52.84 E-value: 1.51e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAAARRRRSDPYVKSYLLPDKQSKR--KTAVKKRNLNPVFNETLRYSVPQAELQGRVLsLSVWHRESLGR 360
Cdd:cd08685   14 LTLHVLEAKGLRSTNSGTCNSYVKISLSPDKEVRFrqKTSTVPDSANPLFHETFSFDVNERDYQKRLL-VTVWNKLSKSR 92


                 ....
gi 300863107 361 NIFL 364
Cdd:cd08685   93 DSGL 96

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175996 [Multi-domain] Cd Length: 127 Bit Score: 52.66 E-value: 2.09e-08

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 300863107 428 VKEARDLLPLRA-GSLDTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTMVYDgFGPADLRQ 489
Cdd:cd04030   22 VHKCRNLPPCDSsDIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFP-VSLEELKR 83

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175999 [Multi-domain] Cd Length: 133 Bit Score: 52.74 E-value: 2.71e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAaarrRR-----SDPYVKSYLLPDKQSKR----KTAVKKRNLNPVFNETLRYSVPQAELQgrvLSLSVW 353
Cdd:cd04033    2 LRVKVLAGIDLA----KKdifgaSDPYVKISLYDPDGNGEidsvQTKTIKKTLNPKWNEEFFFRVNPREHR---LLFEVF 74

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 300863107 354 HRESLGRNIFLGEVEVPL-------DTWDWGSEPTWLPLQPRVPPSpddlPSRGLLALSLKYV 409
Cdd:cd04033   75 DENRLTRDDFLGQVEVPLnnlptetPGNERRYTFKDYLLRPRSSKS----RVKGHLRLYMAYL 133

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.

Pssm-ID: 176002 [Multi-domain] Cd Length: 124 Bit Score: 52.17 E-value: 3.65e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 284 RVHVIQCQGLAAARRR-RSDPYVKSYLLPDKQSKRKTAVKKrNLNPVFNET--LRYSVPQAELqgrvLSLSVWHRESLGR 360
Cdd:cd04037    3 RVYVVRARNLQPKDPNgKSDPYLKIKLGKKKINDRDNYIPN-TLNPVFGKMfeLEATLPGNSI----LKISVMDYDLLGS 77


                 ....*.
gi 300863107 361 NIFLGE 366
Cdd:cd04037   78 DDLIGE 83

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 175991 [Multi-domain] Cd Length: 123 Bit Score: 51.72 E-value: 4.47e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAAARRR-RSDPYVKSYLlpdKQSKRKTAVKKRNLNPVFNETLRYSVPQAELQgrVLSLSVWHRESLGRN 361
Cdd:cd04025    2 LRCHVLEARDLAPKDRNgTSDPFVRVFY---NGQTLETSVVKKSCYPRWNEVFEFELMEGADS--PLSVEVWDWDLVSKN 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 300863107 362 IFLGEVEVPLDTWDWGSEPT-WLPLQPRVPPSPDDLPSRGLLALSLK 407
Cdd:cd04025   77 DFLGKVVFSIQTLQQAKQEEgWFRLLPDPRAEEESGGNLGSLRLKVR 123

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 175995 [Multi-domain] Cd Length: 125 Bit Score: 51.67 E-value: 4.55e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 420 PSGELHFWVKEARDLL---PLRAGSlDTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTMVYDgFGPADLRQACAELSL 496
Cdd:cd04029   13 KTQSLNVHVKECRNLAygdEAKKRS-NPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYS-ISHSQLETRTLQLSV 90

                         90       100
                 ....*....|....*....|.
gi 300863107 497 WDHGALA-NRQLGGTRLSLGT 516
Cdd:cd04029   91 WHYDRFGrNTFLGEVEIPLDS 111

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 51.77 E-value: 4.69e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGL---AAARRRRSDPYVKSYLL---PDKQSKRKTAVKKRN-LNPVFNETLRYSVPQAELQgrVLSLSVWHr 355
Cdd:cd00275    4 LTIKIISGQQLpkpKGDKGSIVDPYVEVEIHglpADDSAKFKTKVVKNNgFNPVWNETFEFDVTVPELA--FLRFVVYD- 80

                         90
                 ....*....|....*..
gi 300863107 356 ESLGRNIFLGEVEVPLD 372
Cdd:cd00275   81 EDSGDDDFLGQACLPLD 97

C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176054 [Multi-domain] Cd Length: 137 Bit Score: 51.57 E-value: 7.18e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 399 RGLLALSLKYVPAgsegaglppSGELHFWVKEARDLLPLRAGSLDTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTMV 478
Cdd:cd08409    1 LGDIQISLTYNPT---------LNRLTVVVLRARGLRQLDHAHTSVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNESFS 71

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 300863107 479 YdGFGPADLRQACAELSLWDHGAL-ANRQLGgtRLSLGtgssyglqvPWMDSTPEEKQLWQALLEQPCEWV 548
Cdd:cd08409   72 F-KVTSRQLDTASLSLSVMQSGGVrKSKLLG--RVVLG---------PFMYARGKELEHWNDMLSKPKELI 130

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176050 [Multi-domain] Cd Length: 136 Bit Score: 51.65 E-value: 7.53e-08

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 399 RGLLALSLKYVPAgsegaglppSGELHFWVKEARDLLPLR-AGSLDTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTM 477
Cdd:cd08405    1 RGELLLSLCYNPT---------ANRITVNIIKARNLKAMDiNGTSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESF 71

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 300863107 478 VYDgfGPAD-LRQACAELSLWDHGALANRQLGGtRLSLGTgssyglqvpwmDSTPEEKQLWQALLEQP 544
Cdd:cd08405   72 IFN--IPLErLRETTLIITVMDKDRLSRNDLIG-KIYLGW-----------KSGGLELKHWKDMLSKP 125

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 50.79 E-value: 1.14e-07

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 300863107 424 LHFWVKEARDLlPLR--AGSLDTYVQCFVLPDDSQasRQRTRVVRRSLSPVFNHTMVYDGF 482
Cdd:cd08386   18 LTLKILKAVEL-PAKdfSGTSDPFVKIYLLPDKKH--KLETKVKRKNLNPHWNETFLFEGF 75

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 52.45 E-value: 7.04e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107  276 YEPgAAELRVHVIQCQGLAAARRR-RSDPYVKsYLLPDKqSKRKTAVKKRNLNPVFNETLRYSVPQAELQgrVLSLSVWH 354
Cdd:COG5038  1036 VEN-SGYLTIMLRSGENLPSSDENgYSDPFVK-LFLNEK-SVYKTKVVKKTLNPVWNEEFTIEVLNRVKD--VLTINVND 1110

                          90       100
                  ....*....|....*....|....*...
gi 300863107  355 RESLGRNIFLGEVEVPLDTWDWGSEPTW 382
Cdd:COG5038  1111 WDSGEKNDLLGTAEIDLSKLEPGGTTNS 1138

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176049 [Multi-domain] Cd Length: 136 Bit Score: 48.19 E-value: 1.09e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 399 RGLLALSLKYVPAgsegaglppSGELHFWVKEARDLlPLR--AGSLDTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHT 476
Cdd:cd08404    1 RGELLLSLCYQPT---------TNRLTVVVLKARHL-PKMdvSGLADPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNES 70

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 300863107 477 MVYDgfGPAD-LRQACAELSLWDHGALANRQLGGtRLSLGtgssyglqvpwMDSTPEEKQLWQALLEQP 544
Cdd:cd08404   71 FVFD--IPSEeLEDISVEFLVLDSDRVTKNEVIG-RLVLG-----------PKASGSGGHHWKEVCNPP 125

C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador (Sav)/Warts (Wts)/Hippo (Hpo) (SWH) signaling network, which limits tissue growth by inhibiting cell proliferation and promoting apoptosis. The core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylates and inactivates the YAP/Yorkie (Yki) transcription coactivator. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are part of the upstream regulation controlling pathway mechanism. Kibra colocalizes and associates with Mer and Ex and is thought to transduce an extracellular signal via the SWH network. The apical scaffold machinery that contains Hpo, Wts, and Ex recruits Yki to the apical membrane facilitating its inhibitory phosphorlyation by Wts. Since Kibra associates with Ex and is apically located it is hypothesized that KIBRA is part of the scaffold, helps in the Hpo/Wts complex, and helps recruit Yki for inactivation that promotes SWH pathway activity. Kibra contains two amino-terminal WW domains, an internal C2-like domain, and a carboxy-terminal glutamic acid-rich stretch. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176062 Cd Length: 124 Bit Score: 47.61 E-value: 1.23e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 270 VHFALHYEPGAAELRVHVIQCQGLAA-ARRRRSDPYVKSYLLPDKQSKR---KTAVKKRNLNPVFNETLRYSVPQAELQG 345
Cdd:cd08680    3 VQIGLRYDSGDSSLVISVEQLRNLSAlSIPENSKVYVRVALLPCSSSTSclfRTKALEDQDKPVFNEVFRVPISSTKLYQ 82

                         90       100
                 ....*....|....*....|....*.
gi 300863107 346 RVLSLSVWHRESLGRNIFLGEVEVPL 371
Cdd:cd08680   83 KTLQVDVCSVGPDQQEECLGGAQISL 108

C2 domain third repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176010 [Multi-domain] Cd Length: 120 Bit Score: 47.20 E-value: 1.61e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLaaarR-----RRSDPYVKsyLLPDKQSKRKTAVKKRNLNPVFNETLrYsVPQAELqGRVLSLSVWHRES 357
Cdd:cd04045    3 LRLHIRKANDL----KnlegvGKIDPYVR--VLVNGIVKGRTVTISNTLNPVWDEVL-Y-VPVTSP-NQKITLEVMDYEK 73

                         90
                 ....*....|....*
gi 300863107 358 LGRNIFLGEVEVPLD 372
Cdd:cd04045   74 VGKDRSLGSVEINVS 88

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176064 [Multi-domain] Cd Length: 126 Bit Score: 47.06 E-value: 2.08e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 284 RVHVIQCQGL-AAARRRRSDPYVKSYLLPDKQSkrkTAVKKRNLNPVFNETLRYSVPQAELQGR---VLSLSVWHRESLG 359
Cdd:cd08682    2 QVTVLQARGLlCKGKSGTNDAYVIIQLGKEKYS---TSVKEKTTSPVWKEECSFELPGLLSGNGnraTLQLTVMHRNLLG 78

                         90
                 ....*....|...
gi 300863107 360 RNIFLGEVEVPLD 372
Cdd:cd08682   79 LDKFLGQVSIPLN 91

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.

Pssm-ID: 176019 [Multi-domain] Cd Length: 127 Bit Score: 46.86 E-value: 2.30e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLaaarRRRSDPYVKsylLPDKQSKRKTAVKKRNLNPVFNETLRYSVPQAELQGRVLSLSVWHRESLGRNI 362
Cdd:cd08373    1 LVVSLKNLPGL----KGKGDRIAK---VTFRGVKKKTRVLENELNPVWNETFEWPLAGSPDPDESLEIVVKDYEKVGRNR 73


                 ....*....
gi 300863107 363 FLGEVEVPL 371
Cdd:cd08373   74 LIGSATVSL 82

FYVE-type zinc finger; This FYVE-type zinc finger is found at the N-terminus of effector proteins including rabphilin-3A and regulating synaptic membrane exocytosis protein 2.

Pssm-ID: 426716 Cd Length: 118 Bit Score: 46.60 E-value: 2.41e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 300863107   35 SFLTEEEQEAIAGVLQRDARLRQLEEGRVSKLRASVADPGQLKILTGDwfqEARSQRHHNAHFGS 99
Cdd:pfam02318   1 SKLTDEEAEHVWEVVQRDFDLRKKEEERLGELKGKLDKESSKRELLGN---QAHLGETHCIRCLQ 62

C2 domain first repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176058 [Multi-domain] Cd Length: 153 Bit Score: 46.98 E-value: 3.91e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 262 EAVQVRGSVHFAL-----HYEPGAAELRVHVIQCQGLAA-----------------ARRRRSDPYVKSYLLPDKQSKRK- 318
Cdd:cd08676    4 QAFGVSPEEHEALlervrEAEPPIFVLKVTVIEAKGLLAkdvngfsdpycmlgivpASRERNSEKSKKRKSHRKKAVLKd 83

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 300863107 319 ---------TAVKKRNLNPVFNETLRYSVpqAELQGRVLSLSVWHREslgrNIFLGEVEVPLDTWDWGSEPTWLPL 385
Cdd:cd08676   84 tvpaksikvTEVKPQTLNPVWNETFRFEV--EDVSNDQLHLDIWDHD----DDFLGCVNIPLKDLPSCGLDSWFKL 153

C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain either a single C2 domain or two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

Pssm-ID: 176029 [Multi-domain] Cd Length: 117 Bit Score: 45.72 E-value: 4.81e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAAarRRRSDPYVKSYLlpDKQSKRKTAVKKRnLNPVFNETLRYSVPQAELQGRVLSLSVWHRESLGRNI 362
Cdd:cd08383    2 LRLRILEAKNLPS--KGTRDPYCTVSL--DQVEVARTKTVEK-LNPFWGEEFVFDDPPPDVTFFTLSFYNKDKRSKDRDI 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 300863107 363 flGEVEVPLDTWDWGSE-PTWLPLQPRVPPSPDdlpsRGLLALSLKY 408
Cdd:cd08383   77 --VIGKVALSKLDLGQGkDEWFPLTPVDPDSEV----QGSVRLRARY 117

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.

Pssm-ID: 175989 [Multi-domain] Cd Length: 127 Bit Score: 45.79 E-value: 6.40e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 428 VKEARDLLPL-RAGSLDTYVqcfVLPDDSQasRQRTRVVRRSLSPVFNHTMVYDGFGPADLRQACAELSLWDHGALANRQ 506
Cdd:cd04022    6 VVDAQDLMPKdGQGSSSAYV---ELDFDGQ--KKRTRTKPKDLNPVWNEKLVFNVSDPSRLSNLVLEVYVYNDRRSGRRR 80

                         90       100
                 ....*....|....*....|.
gi 300863107 507 --LGGTRLSLGTGSSYGLQVP 525
Cdd:cd04022   81 sfLGRVRISGTSFVPPSEAVV 101

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176031 [Multi-domain] Cd Length: 124 Bit Score: 45.33 E-value: 6.90e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 421 SGELHFWVKEARDLLPLR-AGSLDTYVQCFVLPDDSQasRQRTRVVRRSLSPVFNHTMVYDgFGPADLRQACAELSLWDH 499
Cdd:cd08385   15 SNQLTVGIIQAADLPAMDmGGTSDPYVKVYLLPDKKK--KFETKVHRKTLNPVFNETFTFK-VPYSELGNKTLVFSVYDF 91

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 300863107 500 galaNR-----QLGGTRLSLGTgssyglqvpwmDSTPEEKQLWQALLE 542
Cdd:cd08385   92 ----DRfskhdLIGEVRVPLLT-----------VDLGHVTEEWRDLES 124

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175988 [Multi-domain] Cd Length: 125 Bit Score: 45.35 E-value: 8.80e-06

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 300863107 297 RRRRSDPYVKsyLLPDKQSKRKTAVKKRNLNPVFNETLRYSV-PQAELQGRVLSLSvwhreSLGRNIFLGEVEVPL 371
Cdd:cd04021   18 KSFKPDPYVE--VTVDGQPPKKTEVSKKTSNPKWNEHFTVLVtPQSTLEFKVWSHH-----TLKADVLLGEASLDL 86

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176070 [Multi-domain] Cd Length: 110 Bit Score: 44.99 E-value: 8.97e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAAARRRR--SDPYVKSYLLpdkQSKRKTAVKKRNLNPVFN-ETLRYSVPQAELQGRVLSLSVWHRESLG 359
Cdd:cd08688    1 LKVRVVAARDLPVMDRSSdlTDAFVEVKFG---STTYKTDVVKKSLNPVWNsEWFRFEVDDEELQDEPLQIRVMDHDTYS 77

                         90       100       110
                 ....*....|....*....|....*....|
gi 300863107 360 RNIFLGEVEVPLDTWDWGSEPT----WLPL 385
Cdd:cd08688   78 ANDAIGKVYIDLNPLLLKDSVSqisgWFPI 107

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176034 [Multi-domain] Cd Length: 128 Bit Score: 44.65 E-value: 1.39e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 300863107 428 VKEARDLLPLR--AGSLDTYVQCFVLPDdsQASRQRTRVVRRSLSPVFNHTMVYDGFGPADL 487
Cdd:cd08388   22 IIECRDLPAMDeqSGTSDPYVKLQLLPE--KEHKVKTRVLRKTRNPVYDETFTFYGIPYNQL 81

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 44.67 E-value: 1.65e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 300863107 424 LHFWVKEARDLLPLRAGSLDTYVQCFVLPDDSQASRqRTRVVRRSLSPVFNHTMVYDGFGPAD 486
Cdd:cd08675    1 LSVRVLECRDLALKSNGTCDPFARVTLNYSSKTDTK-RTKVKKKTNNPRFDEAFYFELTIGFS 62

C2 domain second repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium and this is indeed the case here. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176053 [Multi-domain] Cd Length: 138 Bit Score: 44.67 E-value: 1.79e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 274 LHYEPGAAELRVHVIQCQGLA-AARRRRSDPYVKSYLL-PDKQ--SKRKTAVKKRNLNPVFNETLRYSVPQAELQGRVLS 349
Cdd:cd08408    8 LEYNALTGRLSVEVIKGSNFKnLAMNKAPDTYVKLTLLnSDGQeiSKSKTSIRRGQPDPEFKETFVFQVALFQLSEVTLM 87

                         90       100
                 ....*....|....*....|....
gi 300863107 350 LSVWHRESLGRNIFLGEVEVPLDT 373
Cdd:cd08408   88 FSVYNKRKMKRKEMIGWFSLGLNS 111

C2 domain in Protein Kinase C (PKC) epsilon; A single C2 domain is found in PKC epsilon. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1 (alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.

Pssm-ID: 175981 [Multi-domain] Cd Length: 132 Bit Score: 43.80 E-value: 3.38e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGL---AAARRRRS--------DPYVKSYLlpDKQSKRKTAVKKRNLNPVFNETLRYSVPqaelQGRVLSLS 351
Cdd:cd04014    6 LKIKICEAVDLkptDWSTRHAVpkkgsqllDPYVSIDV--DDTHIGKTSTKPKTNSPVWNEEFTTEVH----NGRNLELT 79

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 300863107 352 VWHRESLGRNIFLGEVEVPLD---TWDWGSEPTWLPLQP 387
Cdd:cd04014   80 VFHDAAIGPDDFVANCTISFEdliQRGSGSFDLWVDLEP 118

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175976 [Multi-domain] Cd Length: 133 Bit Score: 43.77 E-value: 3.63e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 431 ARDLLPLRA-GSLDTYVQCFVLPDD--SQASRQRTRVVRRSLSPVFNHTMVYDgFGPADLRQ--ACAELSLWDHGALANR 505
Cdd:cd04009   25 ARNLLPLDSnGSSDPFVKVELLPRHlfPDVPTPKTQVKKKTLFPLFDESFEFN-VPPEQCSVegALLLFTVKDYDLLGSN 103


                 ....
gi 300863107 506 QLGG 509
Cdd:cd04009  104 DFEG 107

C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. Little is known about the expression or localization of Slp3. The C2A domain of Slp3 is Ca2+ dependent. It has been demonstrated that Slp3 promotes dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176038 [Multi-domain] Cd Length: 128 Bit Score: 43.66 E-value: 3.80e-05

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 300863107 445 YVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTMVYDgFGPADLRQACAELSLWDHGALANR 505
Cdd:cd08392   40 YVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYV-VEADLLSSRQLQVSVWHSRTLKRR 99

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176033 [Multi-domain] Cd Length: 124 Bit Score: 42.78 E-value: 6.80e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 398 SRGLLALSLKYVPagsegaglpPSGELHFWVKEARDLLPLR-AGSLDTYVQCFVLPDDSQAsrQRTRVVRRSLSPVFNHT 476
Cdd:cd08387    1 TRGELHFSLEYDK---------DMGILNVKLIQARNLQPRDfSGTADPYCKVRLLPDRSNT--KQSKIHKKTLNPEFDES 69

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 300863107 477 MVYdGFGPADLRQACAELSLWDHGALA-NRQLGGTRLSL 514
Cdd:cd08387   70 FVF-EVPPQELPKRTLEVLLYDFDQFSrDECIGVVELPL 107

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176047 [Multi-domain] Cd Length: 136 Bit Score: 42.77 E-value: 7.40e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 400 GLLALSLKYVPAgsegaglppSGELHFWVKEARDLLPLRAGSL-DTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTMV 478
Cdd:cd08402    2 GDICFSLRYVPT---------AGKLTVVILEAKNLKKMDVGGLsDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFS 72

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 300863107 479 YDgFGPADLRQACAELSLWDHGALA-NRQLGgtRLSLGTGSSYGLQVPWMD 528
Cdd:cd08402   73 FE-VPFEQIQKVHLIVTVLDYDRIGkNDPIG--KVVLGCNATGAELRHWSD 120

C2 domain second repeat present in Synaptotagmin 13; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 13, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 12, does not have any consensus Ca2+ binding sites. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176052 [Multi-domain] Cd Length: 138 Bit Score: 43.05 E-value: 7.55e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 268 GSVHFALHYEPGAAELRVHVIQCQGLAAARRRR---SDPYVKSYL------LPDKQSKRKtavkKRNLNPVFNETLRYSV 338
Cdd:cd08407    2 GEVLLSISYLPAANRLLVVVIKAKNLHSDQLKLllgIDVSVKVTLkhqnakLKKKQTKRA----KHKINPVWNEMIMFEL 77

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 300863107 339 PQAELQGRVLSLSVWHRESLGRNIFLGEVEVPLDT 373
Cdd:cd08407   78 PSELLAASSVELEVLNQDSPGQSLPLGRCSLGLHT 112

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176022 [Multi-domain] Cd Length: 116 Bit Score: 41.47 E-value: 1.30e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 300863107 301 SDPYVKSYLlpdKQSKRKTAVKKRNLNPVFNEtlRYSVPQAELQGRVLSLSVWHRESLGRNIFLGEVEVPLDT 373
Cdd:cd08376   21 SDPYVKFRL---GNEKYKSKVCSKTLNPQWLE--QFDLHLFDDQSQILEIEVWDKDTGKKDEFIGRCEIDLSA 88

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176060 [Multi-domain] Cd Length: 126 Bit Score: 41.58 E-value: 1.80e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAAARRRrSDPYVkSYLLPDKQSKRKTAVKKRNLNPVFNETLRYsvpqaELQGR--VLSLSVWHRESLGR 360
Cdd:cd08678    1 LLVKNIKANGLSEAAGS-SNPYC-VLEMDEPPQKYQSSTQKNTSNPFWDEHFLF-----ELSPNskELLFEVYDNGKKSD 73

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 300863107 361 NIFLGEVEVPLDTWDWG-SEPTWLPLQPRvpPSPDDlPSRGLLALSLKYVPAG 412
Cdd:cd08678   74 SKFLGLAIVPFDELRKNpSGRQIFPLQGR--PYEGD-SVSGSITVEFLFMEPA 123

C2 domain second repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176012 [Multi-domain] Cd Length: 110 Bit Score: 41.01 E-value: 2.00e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 300 RSDPYVKSY-LLPDKQSK--RKTAVKKRNLNPVFNEtlrYSVPQAEL----QGRVLSLSVWHRESLGRNIFLGEVEVPLD 372
Cdd:cd04047   20 KSDPFLEISrQSEDGTWVlvYRTEVIKNTLNPVWKP---FTIPLQKLcngdYDRPIKIEVYDYDSSGKHDLIGEFETTLD 96

hypothetical protein; Provisional

Pssm-ID: 223003 [Multi-domain] Cd Length: 413 Bit Score: 43.81 E-value: 2.15e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107  62 RVSKLRASVADPGQLKILTGDWFQEARSQRHHNAHFGSDLVRASMRRKKSTRGDQAPGHDREAEA---------AVKEKE 132
Cdd:PHA03169  36 RRGTAARAAKPAPPAPTTSGPQVRAVAEQGHRQTESDTETAEESRHGEKEERGQGGPSGSGSESVgsptpspsgSAEELA 115

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 133 EGPEPRLTIDEAPQERLRETEGPDFPSPSVPLKASDPEEASqaqEDPGQGDQQVCAEEADPELEPASGGEQEPRPQQAQT 212
Cdd:PHA03169 116 SGLSPENTSGSSPESPASHSPPPSPPSHPGPHEPAPPESHN---PSPNQQPSSFLQPSHEDSPEEPEPPTSEPEPDSPGP 192

                        170
                 ....*....|....*..
gi 300863107 213 KAASQILENGEEAPGPD 229
Cdd:PHA03169 193 PQSETPTSSPPPQSPPD 209

hypothetical protein; Provisional

Pssm-ID: 223003 [Multi-domain] Cd Length: 413 Bit Score: 43.81 E-value: 2.35e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 118 PGHDREAEAAVKEKEEGPEprltiDEAPQERLREtEGPDFPSPSVPLKASDPEEASQAQEDPGQGDQQVCAEEADPELEP 197
Cdd:PHA03169 141 PSHPGPHEPAPPESHNPSP-----NQQPSSFLQP-SHEDSPEEPEPPTSEPEPDSPGPPQSETPTSSPPPQSPPDEPGEP 214

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 300863107 198 ASGGEQEPRPQQAQTKAASQILENGEEAPGPDPSLDR 234
Cdd:PHA03169 215 QSPTPQQAPSPNTQQAVEHEDEPTEPEREGPPFPGHR 251

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176048 [Multi-domain] Cd Length: 134 Bit Score: 40.95 E-value: 3.14e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 400 GLLALSLKYvpagsegagLPPSGELHFWVKEARDLLPLR-AGSLDTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTMV 478
Cdd:cd08403    1 GELMFSLCY---------LPTAGRLTLTIIKARNLKAMDiTGFSDPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEALV 71

                         90       100       110
                 ....*....|....*....|....*....|.
gi 300863107 479 YDgFGPADLRQACAELSLWDHGALANRQLGG 509
Cdd:cd08403   72 FD-VPPENVDNVSLIIAVVDYDRVGHNELIG 101

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.

Pssm-ID: 176007 [Multi-domain] Cd Length: 121 Bit Score: 40.72 E-value: 3.32e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAAarRRR---SDPYVKsYLLPDKQS-KRKTAVKkrNLNPVFNETlrYSVPQAELQgRVLSLSVWHRESL 358
Cdd:cd04042    2 LDIHLKEGRNLAA--RDRggtSDPYVK-FKYGGKTVyKSKTIYK--NLNPVWDEK--FTLPIEDVT-QPLYIKVFDYDRG 73

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 300863107 359 GRNIFLGEVEVPLDTWDWGsEPTWLPLQPRVPPSPDDLpsrGLLALSLKYVP 410
Cdd:cd04042   74 LTDDFMGSAFVDLSTLELN-KPTEVKLKLEDPNSDEDL---GYISLVVTLTP 121

C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 40.60 E-value: 3.66e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 282 ELRVHVIQCQGLAAARRRR-SDPYVK-SYLlpdKQSKrKTAVKKRNLNPVFNETLRYsvPQAELQGR---------VLSL 350
Cdd:cd04017    2 QLRAYIYQARDLLAADKSGlSDPFARvSFL---NQSQ-ETEVIKETLSPTWDQTLIF--DEVELYGSpeeiaqnppLVVV 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 300863107 351 SVWHRESLGRNIFLGE-VEVPL----DTWDWGSEPTWLPL 385
Cdd:cd04017   76 ELFDQDSVGKDEFLGRsVAKPLvkldLEEDFPPKLQWFPI 115

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176036 [Multi-domain] Cd Length: 123 Bit Score: 40.32 E-value: 3.74e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 300863107 422 GELHFWVK-------------EARDLLPLRAGSL--DTYVQCFVLPDDSQaSRQrTRVVRRSLSPVFNHTMVYD 480
Cdd:cd08390    1 GRLWFSVQydleeeqltvsliKARNLPPRTKDVAhcDPFVKVCLLPDERR-SLQ-SKVKRKTQNPNFDETFVFQ 72

C2 domain first repeat present in RasA2 and RasA3; RasA2 and RasA3 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA2 and RasA3 are both inositol 1,3,4,5-tetrakisphosphate-binding proteins and contain an N-terminal C2 domain, a Ras-GAP domain, a pleckstrin-homology (PH) domain which localizes it to the plasma membrane, and Bruton's Tyrosine Kinase (BTK) a zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176046 [Multi-domain] Cd Length: 121 Bit Score: 40.11 E-value: 4.28e-04

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 300863107 312 DKQSKRKTAVKKRNLNPVFNETLRYSVPQaelQGRVLSLSVWHRESLGRNIFLGEVEVPL-DTWDWGSEPTWLPLQP 387
Cdd:cd08401   31 DQEEVFRTKTVEKSLCPFFGEDFYFEIPR---TFRHLSFYIYDRDVLRRDSVIGKVAIKKeDLHKYYGKDTWFPLQP 104

C2 domain; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 13, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 12, does not have any consensus Ca2+ binding sites. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This CD contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176059 Cd Length: 118 Bit Score: 40.28 E-value: 4.50e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 270 VHFALHYEPGAAELrvHVIQCQGLAAARRRRSDPYVKSYLLPDKQSKR-KTAVKKRNLNPVFNETLRYSVPQAELQGRVL 348
Cdd:cd08677    3 LHYSLSYDKQKAEL--HVNILEAENISVDAGCECYISGCVSVSEGQKEaQTALKKLALHTQWEEELVFPLPEEESLDGTL 80

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 300863107 349 SLSVWHRESLGRNIFLGE-------VEVPLDTWDWG 377
Cdd:cd08677   81 TLTLRCCDRFSRHSTLGElrlkladVSMMLGAAQWV 116

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176008 [Multi-domain] Cd Length: 126 Bit Score: 39.55 E-value: 7.36e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 285 VHVIQCQGLAAARR-RRSDPYVksyLLPDKQSKR---KTAVKKRNLNPVFNETLRYSVPQAElqGRVLSLSVWHRESLGR 360
Cdd:cd04043    5 IRIVRAENLKADSSnGLSDPYV---TLVDTNGKRriaKTRTIYDTLNPRWDEEFELEVPAGE--PLWISATVWDRSFVGK 79

                         90       100       110
                 ....*....|....*....|....*....|..
gi 300863107 361 NIFLGEVEVPLDTW---DWG-SEPTWLPLQPR 388
Cdd:cd04043   80 HDLCGRASLKLDPKrfgDDGlPREIWLDLDTQ 111

C2 domain of Perforin; Perforin contains a single copy of a C2 domain in its C-terminus and plays a role in lymphocyte-mediated cytotoxicity. Mutations in perforin leads to familial hemophagocytic lymphohistiocytosis type 2. The function of perforin is calcium dependent and the C2 domain is thought to confer this binding to target cell membranes. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175998 [Multi-domain] Cd Length: 127 Bit Score: 39.55 E-value: 8.18e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 277 EPGAAELRVHVIQCQGLAAARRRRSDPYVKSYLlpDKQSKRkTAVKKRNLNPVFNETLRY-SVpqaEL-QGRVLSLSVWH 354
Cdd:cd04032   24 RRGLATLTVTVLRATGLWGDYFTSTDGYVKVFF--GGQEKR-TEVIWNNNNPRWNATFDFgSV---ELsPGGKLRFEVWD 97

                         90
                 ....*....|....*...
gi 300863107 355 RESLGRNIFLGEVEVPLD 372
Cdd:cd04032   98 RDNGWDDDLLGTCSVVPE 115

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176024 [Multi-domain] Cd Length: 121 Bit Score: 39.22 E-value: 1.16e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAAARrrrSDPYVKSYLLPDKQSKRKTavkKRNLNPVFNETLRYSvpQAELQGRVLSLSVWHRESLGrNI 362
Cdd:cd08378    2 LYVRVVKARGLPANS---NDPVVEVKLGNYKGSTKAI---ERTSNPEWNQVFAFS--KDRLQGSTLEVSVWDKDKAK-DD 72

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 300863107 363 FLGEV-----EVPLdtwdwgseptwlplqpRVPP-SP 393
Cdd:cd08378   73 FLGGVcfdlsEVPT----------------RVPPdSP 93

C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 12, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 13, do not have any consensus Ca2+ binding sites. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176051 [Multi-domain] Cd Length: 136 Bit Score: 39.00 E-value: 1.47e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 400 GLLALSLKYvpagsegagLPPSGELHFWVKEARDL-LPLRAGSLDTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTMV 478
Cdd:cd08406    2 GEILLSLSY---------LPTAERLTVVVVKARNLvWDNGKTTADPFVKVYLLQDGRKISKKKTSVKRDDTNPIFNEAMI 72


                 .
gi 300863107 479 Y 479
Cdd:cd08406   73 F 73

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. The members here have topology I.

Pssm-ID: 176021 [Multi-domain] Cd Length: 136 Bit Score: 38.90 E-value: 1.96e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 279 GAAELRVHVIQCQGLAAARRR-RSDPYVKSYLlpDKQSKrKTAVKKRNLNPVFNETLRYSVpqAELQGRVLSLSVWHRES 357
Cdd:cd08375   13 GIGRLMVVIVEGRDLKPCNSNgKSDPYCEVSM--GSQEH-KTKVVSDTLNPKWNSSMQFFV--KDLEQDVLCITVFDRDF 87

                         90
                 ....*....|....
gi 300863107 358 LGRNIFLGEVEVPL 371
Cdd:cd08375   88 FSPDDFLGRTEIRV 101

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the C2 domain. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176067 [Multi-domain] Cd Length: 119 Bit Score: 38.20 E-value: 2.20e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 300863107 428 VKEARDLLPLRAGSLDTYVQCFVLPDDSQASRQRTRVVRRSLSPVFNHTMVYD 480
Cdd:cd08685   18 VLEAKGLRSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFD 70

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 175993 [Multi-domain] Cd Length: 127 Bit Score: 38.32 E-value: 2.26e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 300863107 281 AELRVHVIQCQGLAAARRR-RSDPYVKSYLlpdKQSKRKTAVKKRNLNPVFNETLRY 336
Cdd:cd04027    1 AKISITVVCAQGLIAKDKTgTSDPYVTVQV---GKTKKRTKTIPQNLNPVWNEKFHF 54

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.

Pssm-ID: 176009 [Multi-domain] Cd Length: 124 Bit Score: 38.30 E-value: 2.47e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLaaarRRRS------DPYVkSYLLPDKQSKRKTAVKKRNLNPVFNETLRysVPQAELQGrVLSLSVWHRE 356
Cdd:cd04044    4 LAVTIKSARGL----KGSDiiggtvDPYV-TFSISNRRELARTKVKKDTSNPVWNETKY--ILVNSLTE-PLNLTVYDFN 75

                         90
                 ....*....|....*..
gi 300863107 357 SLGRNIFLGEVEVPLDT 373
Cdd:cd04044   76 DKRKDKLIGTAEFDLSS 92

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176023 [Multi-domain] Cd Length: 119 Bit Score: 37.66 E-value: 3.18e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 283 LRVHVIQCQGLAAARRR-RSDPYVKSYLLPDKQSKRkTAVKkrNLNPVFNETLRYSVPQAElqgRVLSLSVWHRESLGRN 361
Cdd:cd08377    3 LQVKVIRASGLAAADIGgKSDPFCVLELVNARLQTH-TIYK--TLNPEWNKIFTFPIKDIH---DVLEVTVYDEDKDKKP 76

                         90
                 ....*....|
gi 300863107 362 IFLGEVEVPL 371
Cdd:cd08377   77 EFLGKVAIPL 86

C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fourth C2 repeat, C2D, and has a type-II topology.

Pssm-ID: 175984 [Multi-domain] Cd Length: 135 Bit Score: 37.14 E-value: 5.93e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 423 ELHFWVKEARDLLPL-RAGSLDTYVQCFVLpddSQAsrQRTRVVRRSLSPVFNHTMVYDGF----GPADLRQACAELS-- 495
Cdd:cd04017    2 QLRAYIYQARDLLAAdKSGLSDPFARVSFL---NQS--QETEVIKETLSPTWDQTLIFDEVelygSPEEIAQNPPLVVve 76


                 ....
gi 300863107 496 LWDH 499
Cdd:cd04017   77 LFDQ 80

chromosomal replication initiator protein DnaA;

Pssm-ID: 237605 [Multi-domain] Cd Length: 617 Bit Score: 38.65 E-value: 9.89e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 300863107 103 RASMRRKKSTRGDQAPGHDREAEAAVKEKEEGPEPRLTIDEAPQ-ERLRETEGPDFPSPsvplkASDPEEASQAQEDPGQ 181
Cdd:PRK14086 125 RADDRPPGLPRQDQLPTARPAYPAYQQRPEPGAWPRAADDYGWQqQRLGFPPRAPYASP-----ASYAPEQERDREPYDA 199

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 300863107 182 GDqqvcaeeadPELEPASGGEQEPRPQQAQtkaasqilENGEEAPGPDPS 231
Cdd:PRK14086 200 GR---------PEYDQRRRDYDHPRPDWDR--------PRRDRTDRPEPP 232